Intra-individual variation and sex differences in gene expression of cytochromes P450 in circulating leukocytes.

To clarify partly inconsistent results in gene expression of cytochromes P450 (CYP) in the circulation, we undertook a systematic study over a long time period in 19 healthy men and women. CYP specific mRNA for 1A2, 1B1, 2E1 and 3A4 was studied in the leukocytes collected repeatedly on 20 occasions over a 10-week period. Our study revealed a varying pattern of CYP expression over time. CYP3A4 specific mRNA exhibited the largest intra-individual variation with an average coefficient of variation between 40 and 250%. CYP1B1 and CYP2E1 did not vary as much (39-110%). CYP1A2 was sporadically detected in only ten individuals, but varied considerably when measurable (61-256%). The expression in CYP1B1 was significantly higher in women than in men (P = 0.02). We conclude that CYP gene expression in blood varies considerably over time. It is conceivable that the variation reflects a hitherto unknown influence of exogenous or endogenous factors such as hormones, cytokines, and other circulating factors on the hematogeneous cytochromes.